%0 Journal Article
%T Testing the thrifty gene hypothesis: the Gly482Ser variant in PPARGC1A is associated with BMI in Tongans
%A Sean Myles
%A Rod A Lea
%A Jun Ohashi
%A Geoff K Chambers
%A Joerg G Weiss
%A Emilie Hardouin
%A Johannes Engelken
%A Donia P Macartney-Coxson
%A David A Eccles
%A Izumi Naka
%A Ryosuke Kimura
%A Tsukasa Inaoka
%A Yasuhiro Matsumura
%A Mark Stoneking
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-10
%X Here we examine whether PPARGC1A is a thrifty gene in Pacific populations by testing for an association between Gly482Ser genotypes and BMI in two Pacific populations (Maori and Tongans) and by evaluating the frequency of the risk allele of the Gly482Ser variant in a sample of worldwide populations.We find that the Gly482Ser variant is associated with BMI in Tongans but not in Maori. In a sample of 58 populations worldwide, we also show that the 482Ser risk allele reaches its highest frequency in the Pacific.The association between Gly482Ser genotypes and BMI in Tongans together with the worldwide frequency distribution of the Gly482Ser risk allele suggests that PPARGC1A remains a candidate thrifty gene in Pacific populations.The prevalence of type 2 diabetes mellitus (T2DM) in Polynesians is among the highest in the world, reaching 40% among adults on some islands [1-3]. The thrifty gene hypothesis [4] offers a possible explanation for the high prevalence of T2DM in the Pacific. This hypothesis suggests that populations whose ancestral environments were characterized by periods of feast and famine experienced positive selection for alleles that promote the storage of fat and energy. Moreover, under modern conditions, populations with such thrifty metabolisms are expected to have high rates of T2DM and related traits (e.g. obesity). The ancestors of present-day Polynesians embarked on long open ocean voyages and are believed to have been exposed to cold stress and starvation during their settlement of the Pacific. Such conditions may have driven thrifty alleles to high frequency in Polynesians, thereby explaining the high prevalence of T2DM and obesity in Polynesia today [5-7].According to this hypothesis, T2DM risk alleles at unusually high frequencies in Polynesians would represent strong candidate thrifty alleles: they may have been driven to high frequency by positive selection, thereby accounting for the high prevalence of T2DM in Polynesia. Alternatively, T2DM
%U http://www.biomedcentral.com/1471-2350/12/10